Margination and stretching of von Willebrand factor in the blood stream enable adhesion

Abstract

The protein von Willebrand factor (VWF) is essential in primary hemostasis, as it mediates platelet adhesion to vessel walls. VWF retains its compact (globule-like) shape in equilibrium due to internal molecular associations, but is able to stretch when a high enough shear stress is applied. Even though the shear-flow sensitivity of VWF conformation is well accepted, the behavior of VWF under realistic blood flow conditions remains poorly understood. We perform mesoscopic numerical simulations together with microfluidic experiments in order to characterize VWF behavior in blood flow for a wide range of flow-rate and hematocrit conditions. In particular, our results demonstrate that the compact shape of VWF is important for its migration (or margination) toward vessel walls and that VWF stretches primarily in a near-wall region in blood flow making its adhesion possible. Our results show that VWF is a highly optimized protein in terms of its size and internal associations which are necessary to achieve its vital function. A better understanding of the relevant mechanisms for VWF behavior in microcirculation provides a further step toward the elucidation of the role of mutations in various VWF-related diseases.